'Unqualified success' and 'unmitigated failure': number-needed-to-treat-related concepts for assessing treatment efficacy in the presence of treatment-induced adverse events.

BACKGROUND: Common indices for the quantal assessment of treatment efficacy are reviewed. The absolute risk reduction is a practical index for public health considerations. Its reciprocal has been termed the 'Number Needed to Treat' (NNT), representing the health effort that must on average be expended to accomplish one tangible treatment target. We extend the NNT to evaluate outcome combinations of treatment benefits versus treatment harms.
METHODS: We describe the mathematical context of the NNT, and extend it to evaluate outcome combinations (treatment success/failure with/without treatment-induced adverse effects) in a treated population. These extensions are carried out assuming either independence or positive association between treatment benefit and treatment harm. A method is provided for calculating the standard errors of these extended NNT values. Applications to cost-effectiveness analysis are discussed.
RESULTS: We calculate NNT in three recent therapeutic studies. The results of a trial of the prevention of strokes with warfarin in patients with non-valvular atrial fibrillation are analysed to evaluate treatment success (stroke prevention) against treatment-induced bleeds. An NNT-related cost-benefit analysis is also carried out. We also analyse the results of a study of two modalities of chemotherapeutic treatment in small-cell lung cancer, and of two modalities of surgical intervention in the treatment of cholelithiasis.
CONCLUSIONS: The NNT are useful in direct evaluation of outcome-specific treatment benefits versus treatment-induced harms. They may also be used in cost-effectiveness analyses and are helpful in guiding public health programmes towards the identification of optimal treatment strategies.